Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma
Authors: Ling-Long Tang, Rui Guo, Ning Zhang, Bin Deng, Lei Chen, Zhi-Bin Cheng, Jing Huang, Wei-Han Hu, Shao Hui Huang, Wei-Jun Luo, Jin-Hui Liang, Yu-Ming Zheng, Fan Zhang, Yan-Ping Mao, Wen-Fei Li, Guan-Qun Zhou, Xu Liu, Yu-Pei Chen, Cheng Xu, Li Lin, Qing Liu, Xiao-Jing Du, Yuan Zhang, Ying Sun, Jun Ma
Journal: JAMA (2022)

<h3>Importance</h3> Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). <h3>Objective</h3> To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. <h3>Design, Setting, and Participants</h3> This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes &lt;3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA &lt;4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. <h3>Interventions</h3> Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m<sup>2</sup>every 3 weeks for 3 cycles [n = 169]). <h3>Main Outcomes and Measures</h3> The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). <h3>Results</h3> Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, −1.4%; 1-sided 95% CI, −7.4% to ∞;<i>P</i>value for noninferiority, &lt;.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, −29% [95% CI, −39% to −20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. <h3>Conclusions and Relevance</h3> Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02633202